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2007 ; 401
(2
): 505-13
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SLC41A2 encodes a plasma-membrane Mg2+ transporter
#MMPMID16984228
Sahni J
; Nelson B
; Scharenberg AM
Biochem J
2007[Jan]; 401
(2
): 505-13
PMID16984228
show ga
The TRPM7 (transient receptor potential melastatin 7) ion channel has been
implicated in the uptake of Mg2+ into vertebrate cells, as elimination of TRPM7
expression through gene targeting in DT40 B-lymphocytes renders them unable to
grow in the absence of supplemental Mg2+. However, a residual capacity of
TRPM7-deficient cells to accumulate Mg2+ and proliferate when provided with
supplemental Mg2+ suggests the existence of Mg2+ uptake mechanism(s) other than
TRPM7. Evaluation of the expression of several members of the SLC41 (solute
carrier family 41) family, which exhibit homology with the MgtE class of
prokaryotic putative bivalent-cation transporters, demonstrated that one, SLC41A2
(solute carrier family 41 member 2), is expressed in both wild-type and
TRPM7-deficient DT40 cells. Characterization of heterologously expressed SLC41A2
protein indicated that it is a plasma-membrane protein with an
N-terminus-outside/C-terminus-inside 11-TM (transmembrane)-span topology,
consistent with its functioning as a trans-plasma-membrane transporter. In
contrast with a previous report of ion-channel activity associated with SLC41A2
expression in oocytes, investigation of whole cell currents in SLC41A2-expressing
DT40 cells revealed no novel currents of any type associated with SLC41A2
expression. However, expression of SLC41A2 in TRPM7-deficient cells under the
control of a doxycycline-inducible promoter was able to conditionally enhance
their net uptake of 26Mg2+ and conditionally and dose-dependently provide them
with the capacity to grow in the absence of supplemental Mg2+, observations
strongly supporting a model whereby SLC41A2 directly mediates
trans-plasma-membrane Mg2+ transport. Overall, our results suggest that SLC41A2
functions as a plasma-membrane Mg2+ transporter in vertebrate cells.
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